This project is designed to investigate the pathogenesis and epidemiology of Epstein-Barr virus (EBV)-related lymphoproliferative lesions in AIDS patients: non-Hodgkin lymphoma (NHL) which occurs primarily in adults, and lymphoid interstitial pneumonitis (LIP), which occurs exclusively in children and appears to be associated with a better prognosis than most other opportunistic infections in patients with AIDS. Three specific issues about the pathogenesis of these lesions will be addressed: 1) In addition to EBV, is HIV also present in these lymphoproliferative lesions? 2) Is the EBV in these lesions, latent or replicating? and 3) What specific types of lymphoid cells are present in these lesions and if there is more than one type, is any specific type infected with only EBV, only HIV or both. In addition, we will assess whether there are identifiable epidemiologic factors that are associated with an increased risk of developing EBV-related lymphoproliferative disorders in AIDS patients. To answer these questions, biopsy specimens from AIDS patients with these disorders, both from Yale and from ten other AIDS centers that have agreed to participate will be studied. All specimens will be cultured for EBV and HIV. DNA will be extracted from each specimen and probed for evidence of EBV replication. Protein extracts of the specimens will likewise be probed for replicative EBV antigens as well as for HIV antigens. Histologic sections of each biopsy will be examined by immunofluorescence microscopy and immunoperoxidase staining to determine what types of lymphoid cells are present in each lesion and which cells are infected with EBV, HIV or both. To assess factors that may be associated with the development of these lesions, a group of patients with symptomatic HIV infection but without an EBV-related lymphoproliferative disorder individually matched to the index patients by age, site of care, and presumed mode of acquisition of AIDS, will be selected for comparison. Matched odds ratios and paired T-tests will be calculated to assess associations between the development of these EBV-related lymphoproliferative disorders and a large number of potential clinical epidemiologic risk factors. Similar comparisons will be made for serologic, immunologic and virologic data. Logistic regression will be used to adjust for possible confounders. The sample size will be large enough to have adequate statistical power. These data should help us better understand the epidemiologic risk factors of EBV-associated lymphoproliferative disorders in AIDS.